TABLE 4.

In vitro interaction between itraconazole and terbinafine against S. prolificans

Method and strainResult according to theory
LABIa
Nonparametric [median (range)]Parametricb (α ± 95% CI)NonparametricSemiparametricc
FICi-2FICi-1ΣSYN (n)ΣANT (n)ΣSYN (n)ΣANT (n)
SP48
    78980.13 (0.07-0.16)0.19 (0.13-0.19)4.3 ± 1.319 (2)−20 (1)244 (18)−45 (3)
    79010.52 (0.51-0.52)0.13 (0.13-0.19)9.3 ± 1.836 (3)−25 (2)90 (15)−27 (2)
    79020.07 (0.02-0.56)0.13 (0.13-0.25)203.8 ± 49.149 (4)0 (0)144 (8)0 (0)
    79060.16 (0.04-0.51)0.14 (0.13-0.19)3.3 ± 0.8230 (14)0 (0)291 (16)0 (0)
    79180.51 (0.07-0.51)0.13 (0.09-0.38)25.1 ± 9.652 (5)0 (0)167 (11)0 (0)
        Median0.160.139.34901670
SP72
    78980.13 (0.07-0.56)0.14 (0.13-0.16)25.9 ± 8.276 (6)−31 (2)202 (16)−178 (11)
    79010.75 (0.52-1.00)0.31 (0.31-0.38)57.2 ± 14.710 (1)−85 (4)7 (1)−98 (4)
    79020.02 (0.02-0.28)0.19 (0.07-0.38)182.9 ± 48.141 (4)0 (0)90 (7)0 (0)
    79060.13 (0.06-0.38)0.16 (0.14-0.27)8.1 ± 2.5536 (26)0 (0)428 (23)0 (0)
    79180.51 (0.06-0.52)0.14 (0.09-0.38)457.6 ± 148.581 (8)0 (0)180 (17)0 (0)
        Median0.130.1657.27601800
COL72
    78980.07 (0.02-0.26)0.16 (0.09-0.16)202.9 ± 130.70 (0)−46 (40)0 (0)−109 (8)
    79010.13 (0.01-0.16)0.26 (0.25-0.27)5.2 ± 3.37 (1)−83 (8)0 (0)0 (0)
    79020.13 (0.01-1.02)0.19 (0.14-0.25)29.1 ± 20.510 (1)−53 (4)179 (11)−3 (1)
    79060.04 (0.02-0.13)0.13 (0.09-0.25)23.7 ± 13.76 (1)−209 (26)16 (3)−404 (13)
    79180.16 (0.08-0.26)0.16 (0.13-0.16)69.9 ± 59.7380 (12)0 (0)384 (15)−4 (1)
        Median0.130.1629.17−5316−4
MCOL48
    78980.34 (0.19-0.50)0.27 (0.27-0.28)105.4 ± 39.125 (5)−1 (1)69 (8)0 (0)
    79010.14 (0.13-0.15)0.20 (0.14-0.26)802.1 ± 310.8276 (22)0 (0)417 (20)0 (0)
    79020.27 (0.25-0.28)0.20 (0.16-0.25)23.9 ± 9.4105 (12)0 (0)209 (20)−0 (0)
    79060.20 (0.16-0.25)0.23 (0.19-0.27)81.6 ± 28.031 (4)0 (0)88 (6)0 (0)
    79180.11 (0.06-0.16)0.08 (0.02-0.14)795.3 ± 435.979 (5)0 (0)49 (2)0 (0)
        Median0.200.20105.4790880
MCOL72
    78980.21 (0.14-0.28)0.18 (0.04-0.31)959.7 ± 542.4146 (5)0 (0)529 (18)0 (0)
    79010.04 (0.02-0.07)0.15 (0.05-0.25)5,091.5 ± 3,287.1942 (31)0 (0)372 (15)0 (0)
    79020.30 (0.28-0.31)0.05 (0.04-0.06)404.7 ± 242.3533 (22)0 (0)616 (23)−5 (10)
    79060.28 (0.25-0.31)0.06 (0.05-0.07)2,351.3 ± 1,445.183 (5)0 (0)300 (19)0 (0)
    79180.04 (0.03-0.05)0.07 (0.05-0.09)7,673.7 ± 389.4263 (10)0 (0)1,354 (44)0 (0)
        Median0.210.07959.72630529−16
  • a The median absolute coefficient of variation of the differences between observed and predicted percent growth at each drug combination among replicates of all strains ranged from 58 to 157% (median, 106%) for the SP method, 59 to 222% (median, 106%) for the COL method, and 51 to 69% (median, 61%) for mCOL method with the semiparametric approach and from 57 to 287% (median, 154%) for the SP method, 51 to 195% (median, 115%) for the COL method, and 58 to 89% (median, 71%) for the mCOL method with the non-parametric approach.

  • b The R2 from the nonlinear regression analysis for the fully parametric Greco model ranged from 0.69 to 0.95 (median, 0.88). The IC50s ranged from 0.15 to 93.6 mg/liter (geometric mean, 2.98 mg/liter) of terbinafine and 17.5 × 103 to 7 × 103 mg/liter (geometric mean, 404.4 mg/liter) of itraconazole. The slope (m) ranged from −0.15 to −1.7 (median, −0.68) for terbinafine and −0.16 to −26.7 (median, −0.28) for itraconazole.

  • c The R2 from the nonlinear regression analysis for the Emax model of the semiparametric approach ranged from 0.77 to 0.99 (median, 0.95). The IC50s ranged from 0.23 to 155 mg/liter of terbinafine (geometric mean, 2.85 mg/liter) and from 5.2 to 5011 mg/liter of itraconazole (geometric mean, 298.64 mg/liter). The slope (m) ranged from −0.11 to −1.22 (median, −0.52) for terbinafine and −0.06 to −0.99 (median, −0.43) for itraconazole.